Risk factors and a simple scoring system for predicting bowel resection in infants with NEC

Background and aimsWe intended to investigate the predictors for bowel resection in infants with necrotizing enterocolitis (NEC). We further developed a scoring system for better predicting bowel resection.MethodsA total of 207 infants who underwent surgical management at Children's Hospital, Chongqing Medical University between April 2008 and December 2020 were identified for the following investigation. Bowel resection was reviewed among the infants who underwent the procedure. Potential parameters related to bowel resection were explored using a multiple logistic regression method, and then a scoring system was developed.ResultsAmong the 207 patients who underwent operative intervention that were reviewed, 109 infants underwent bowel resection. Multivariate logistic regression analysis showed that birth weight, hypotension, neutropenia, pneumoperitoneum, acidosis, and intestinal wall thickness were predictors related to the occurrence of bowel resection. A 6-point scoring system was further developed based on the obtained total coefficient, and the infants could be divided into low-, moderate- and high-risk groups according to cut values of 7 and 13.ConclusionThe results of this study demonstrated that severe NEC features and low birth weight were associated with bowel resection. The risk scoring system could accurately separate infants that were suspected to have bowel loss during surgery.     

Effect of deuteration on the single dose pharmacokinetic properties and postoperative analgesic activity of methadone

Although methadone is effective in the management of acute pain, the complexity of its absorption-distribution-metabolism-excretion profile limits its use as an opioid of choice for perioperative analgesia. Because deuteration is known to improve the pharmacokinetic, pharmacodynamic and toxicological properties of some drugs, here we characterized the single dose pharmacokinetic properties and post-operative analgesic efficacy of d₉-methadone.The pharmacokinetic profiles of d₉-methadone and methadone administered intravenously to CD-1 male mice revealed that deuteration leads to a 5.7- and 4.4-fold increase in the area under the time-concentration curve and maximum concentration in plasma, respectively, as well as reduction in clearance (0.9 ± 0.3 L/h/kg vs 4.7 ± 0.8 L/h/kg). The lower brain-to-plasma ratio of d₉-methadone compared to that of methadone (0.35 ± 0.12 vs 2.05 ± 0.62) suggested that deuteration decreases the transfer of the drug across the blood-brain barrier. The estimated LD₅₀ value for a single intravenous dose of d₉-methadone was 2.1-fold higher than that for methadone. Moreover, d₉-methadone outperformed methadone in the efficacy against postoperative pain by primarily activating peripheral opioid receptors. Collectively, these data suggest that the replacement of three hydrogen atoms in three methyl groups of methadone altered its pharmacokinetic properties, improved safety, and enhanced its analgesic efficacy.     

A highly tumor-targeted nanoparticle of podophyllotoxin penetrated tumor core and regressed multidrug resistant tumors

Podophyllotoxin (PPT) exhibited significant activity against P-glycoprotein mediated multidrug resistant (MDR) tumor cell lines; however, due to its poor solubility and high toxicity, PPT cannot be dosed systemically, preventing its clinical use for MDR cancer. We developed a nanoparticle dosage form of PPT by covalently conjugating PPT and polyethylene glycol (PEG) with acetylated carboxymethyl cellulose (CMC-Ac) using one-pot esterification chemistry. The polymer conjugates self-assembled into nanoparticles (NPs) of variable sizes (20–120 nm) depending on the PPT-to-PEG molar ratio (2–20). The conjugate with a low PPT/PEG molar ratio of 2 yielded NPs with a mean diameter of 20 nm and released PPT at ∼5%/day in serum, while conjugates with increased PPT/PEG ratios (5 and 20) produced bigger particles (30 nm and 120 nm respectively) that displayed slower drug release (∼2.5%/day and ∼1%/day respectively). The 20 nm particles exhibited 2- to 5-fold enhanced cell killing potency and 5- to 20-fold increased tumor delivery compared to the larger NPs. The biodistribution of the 20 nm PPT-NPs was highly selective to the tumor with 8-fold higher accumulation than all other examined tissues, while the larger PPT-NPs (30 and 120 nm) exhibited increased liver uptake. Within the tumor, >90% of the 20 nm PPT-NPs penetrated to the hypovascular core, while the larger particles were largely restricted in the hypervascular periphery. The 20 nm PPT-NPs displayed significantly improved efficacy against MDR tumors in mice compared to the larger PPT-NPs, native PPT and the standard taxane chemotherapies, with minimal toxicity.     

Editorial Commentary: Stabilize the Patella to Achieve Functional Gain but Don’t Neglect the Cartilage That May Cause Long-Term Pain! Trochlear Dysplasia Plays a Role in Both

While trochlear dysplasia is commonly discussed as a major risk factor for recurrent patellar instability, it also has a strong relationship with the development of patellofemoral cartilage lesions. Patellofemoral instability frequently occurs in teens and young adults, and the high prevalence of associated cartilage damage unfortunately sets patients up for the progression of degenerative changes of the patellofemoral joint at an early age. The judicious use of magnetic resonance imaging can help identify the presence of chondral lesions, allowing for urgent management of associated osteochondral fractures or open discussions and patient education about the possibility of performing a cartilage restoration procedure concurrently with patellar stabilization surgery. The location and presence of patellofemoral chondral lesions should be considered when contemplating the concurrent use of tibial tubercle osteotomy as part of the patellar stabilization procedure.     

Guidelines for the diagnosis,treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.     

清肾颗粒对慢性肾衰竭患者肾功能及血清α-平滑肌动蛋白和E-钙粘蛋白的影响

目的 观察中药复方清肾颗粒对于慢性肾衰竭湿热证患者肾功能及血清α-平滑肌动蛋白和E-钙粘蛋白的影响。方法 符合纳入标准的70例慢性肾衰竭湿热证患者,随机分为治疗组和对照组各35例,治疗组在对照组治疗方案基础上加用清肾颗粒口服,疗程12周。观察2组中医证候疗效及临床疗效;治疗前后血肌酐（Scr）、肾小球滤过率（eGFR）、血清α-平滑肌动蛋白（α-SMA）、E-钙粘蛋白(E-cadherin)水平变化。结果 研究最终完成68例（治疗组、对照组各34例）。治疗后治疗组中医证候疗效及临床疗效均优于对照组（P<0.05）;治疗组患者Scr、eGFR水平明显改善(P<0.05),优于对照组(P<0.05);治疗组血清α-SMA、E-cadherin水平下降（P<0.05）,比对照组低（P<0.05）;治疗组患者服用清肾颗粒后未出现药物不良副作用。结论 清肾颗粒能够减轻慢性肾衰竭湿热证患者临床症状,降低Scr水平,同时下调慢性肾衰竭湿热证患者血清α-SMA、E-cadherin水平,安全性良好。      

Inflammation and focal atrophy in prostate needle biopsy cores and association to prostatic adenocarcinoma

The possible origin of proliferative inflammatory atrophy in the regenerative proliferation of prostate epithelial cells in response to injury caused by inflammation, and their relation to prostate adenocarcinoma have not been defined. Inflammation and focal atrophy are common pathological findings in prostate biopsies, currently not routinely included in surgical pathology reports. The objective of the study was to determine the correlation between inflammation and focal atrophy with prostate adenocarcinoma. Prostate needle biopsies from 203 patients with clinical parameters suspicious for malignancy were evaluated for the presence and extent of chronic inflammation, type and grade of focal atrophy, high-grade intraepithelial neoplasia, and adenocarcinoma. Relations among them and with age were also analyzed. χ² tests and binary logistic regression were used to estimate associations. Chronic inflammation was observed in 77.3% of the biopsies, significantly associated to adenocarcinoma (P = .031). Moderate/severe inflammation in at least 1 biopsy core increased the risk of prostate adenocarcinoma (odds ratio, 2.94; 95% confidence interval, 1.27-6.8), whereas glandular localization of inflammation decreased the risk. Focal atrophy was present in 72.9% of the biopsies, proliferative inflammatory atrophy was the most common type, and its grade was significantly associated to inflammation (P < .0001) and inflammation intensity (P = .003). An association between prostate adenocarcinoma and inflammation was found, with higher odds in presence of moderate/severe inflammation in at least 1 biopsy core. Increasing grades of proliferative inflammatory atrophy were associated to high levels of inflammation, supporting its previously proposed inflammatory nature.     

方向从脾肾论治肝豆状核变性流涎症举隅

流涎是肝豆状核变性常见的非运动症状,近年来在临床上越来越受到重视。文章总结方向主任多年临床经验,从“脾肾”论治肝豆状核变性患者流涎症,方向主任认为肝豆状核变性流涎症病机在于铜毒内聚,脾肾不足,可在通腑排毒的基础上,配伍健脾化湿,温肾摄唾之品,临床疗效显著。